Ion counting and ion intensity measurements in time‐of‐flight mass spectrometry. Application to matrix‐assisted laser desorption

Abstract

A time-to-digital converter coupled to a charge-to-digital converter has been used to record mass spectra in matrix-assisted laser desorption (MALD) time-of-flight mass spectrometry. Masses above 100 000 Da have been detected by ion counting. Utilizing an electrostatic mirror, good mass resolution has been achieved in MALD. When the number of detected secondary ions is small the sensitivity of mass measurements is improved by using a charge-to-digital converter rather than a transient recorder.Time-of-flight (TOF) mass spectrometry is a very useful method for the study of large proteins and molecular clusters. The new technique of matrix-assisted laser desorption (MALD), suggested by Karas and Hillenkamp,' and by Tanaka et al. ,' is very promising and requires modest experimental facilities. However, the full utilization of the MALD technique for analytical purposes still depends on improvements in mass resolution , mass accuracy, and detection efficiency of large molecular ions.The present experiments were performed in order to gain an understanding of some aspects of the laser desorption mechanism (fragmentation, cluster emission, etc.) and also to evaluate the potential of a new electronic timing device in time-of-flight spectrometry. Several kinds of samples were investigated using different analytical procedures. The molecular mass range of the proteins studied was between -1000 and 70 000 Da. In some cases it was possible to observe the desorption of large clusters of protein molecules. The enhancement of the desorption yield of these large clusters strongly depends on the procedure adopted for sample and target preparation.Different kinds of electronic devices have been developed at the Institut de Physique NuclCaire (IPN) at Orsay, for the time-of-flight mass spectrometer TOF 23.3 Results obtained with a conventional time-todigital converter (TDC) are compared with results obtained using a TDC coupled to a charge-to-digital converter (CDC). The CDC measures the total electric charge associated with each signal of secondary ions arriving on the stop detector (stop signal). This total charge is thus proportional to the number of ions simultaneously hitting the detector. The charge is converted to a digital value which is added to the TOF mass spectrum at the corresponding time value measured by the TDC. A transient waveform recorder has also been used and the results obtained compared with those obtained with the TDC and CDC.It was observed that the mass resolution decreases with the power density of the irradiating laser beam.

A comparison between ion‐to‐photon and microchannel plate detectors

“…The system is described in more detail elsewhere. 11,12 The start signals were obtained by using the complementary fission fragments of 252 Cf impacting on an electron conversion foil. These electrons were accelerated and detected by a second pair of MCPs (MCP start in Fig.…”

Critical factors determining the quantification capability of matrix-assisted laser desorption/ionization– time-of-flight mass spectrometry

“…TDCs are suitable for identifying low-flux ion beams, but ion abundance may be considerably underestimated if high ion flux is present. To achieve the highest analytical performance, it is possible to combine multiple digitizers in series [75,76]. Another novel strategy proposed is the use of an anode array (known as sectioned anodes) to collect electrons generated by MCPs [77,78].…”

Direct quantitative analysis of peptides using matrix assisted laser desorption ionization

“…The decrease of resolution and detection limit (due to poor detector efficiency) [14] in the higher mass range cause poor analyte and internal standard signal-to-noise ratio (S/N), which limits the effective concentration range and measurement accuracy. Postacceleration of ions before detection, use of the optimum analyte/matrix molar ratio, sample preparation (matrix, solvent etc.)…”

“…Sample preparation, matrix crystallization and the conditions of the substrate surface lead to poor intra and inter sample signal reproducibility. In addition low efficiency of the detector ion-to-electron conversion [14], metastable decay in time-of-flight (TOF) instruments [15] and formation of matrix and cationized adducts inducing poor MALDI resolution [16] and sensitivity, all cause both systematic and random measurement errors. Quantitative measurements require a highly linear data acquisition system.…”